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Biotech / Medical : Regeneron Pharmaceuticals -- Ignore unavailable to you. Want to Upgrade?

To: Miljenko Zuanic who wrote (311)	7/23/1999 1:28:00 AM
From: Miljenko Zuanic	Read Replies (1) \| Respond to of 3557

BDNF (as well as GDNF)utility/clinical benefit to ALS pts was never questioned. The issue was BBB. So, if REGN new PIII trial designee give freedom to physician for pt-indovidualy increased/adjusted drug dose to max. tolerated, there is chance that this time results may be sufficient positive. Intrathetal drug administration is OK, but it is not preferential one. From Eureka: eurekalert.org Gene therapy holds promise for treating inherited Lou Gehrig's Disease CHICAGO --- Using gene therapy in laboratory mice, researchers have halted motor neuron destruction and slowed progression of inherited amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, a lethal, progressive neurological disorder that renders the muscles of the body useless while leaving the mind unaffected. This finding suggests that a similar gene therapy approach might someday prove effective in treating humans with ALS, according to Northwestern University developmental neurobiologist Martha C. Bohn and colleagues in an article in the July 15 issue of Human Gene Therapy. Bohn is a professor of pediatrics at Northwestern University Medical School and director of the neurobiology program at Children's Memorial Institute for Education and Research. Into the hindlimbs of an ALS mouse model, Bohn and co-researchers injected young skeletal muscle cells (myoblasts) infected with a virus that had been made harmless and also engineered to carry the gene for glial cell-derived neurotrophic factor (GDNF). GDNF is a protein that has been found to block nerve cell degeneration in animal models of Parkinson's disease. The GDNF gene therapy enhanced survival of motor neurons in the laboratory model of inherited ALS and increased the number of motor neurons that maintained 'communication' with cells in treated leg muscles. Additionally, GDNF gene therapy slowed shrinkage of motor neurons and muscle atrophy, improved motor function in affected mice and delayed onset of ALS disease symptoms. "The most critical issues in designing a gene therapy approach for any human disease are to have a good animal model of the disease and to choose the appropriate target tissue and mode of gene delivery," Bohn said. The mice used in this study express a mutant gene that is carried by humans with a hereditary form of ALS. These mice were developed by Mark Gurney and Teepu Siddique, professor of neurology at Northwestern University Medical School. Due to its unique characteristics, skeletal muscle tissue has raised interest as a target tissue for development of gene therapy to not only treat muscle-specific disorders, but produce enzymes and secreted proteins for treating other tissues, she said. Primary myoblasts can be cultured in large numbers and transduced with foreign genes. After myoblasts are grafted into adult muscles, they maintain the capacity to fuse to host muscle fibers and become incorporated into muscle tissue. "Myoblast-mediated gene therapy would be safer and easier to perform than the conventional method of delivering neurotrophic factors -- injecting large amounts of proteins into the muscle or skin or even directly into the nervous system -- which has been associated with adverse side effects and unsuccessful results," Bohn said. Bohn's approach results in low concentrations of neurotrophic factor being synthesized at the required site of action; that is, the factors are secreted by the muscle cells and are taken up by the terminals of the nerve cells in the spinal cord that control movement. This potentially eliminates the side effects resulting from injection of large amounts of these potent molecules where little of the substance obtains access to the appropriate neurons. Bohn stated that the challenge will be to find a way to safely deliver the GDNF gene in a more global manner to all affected nerve cells and also to ensure that the gene 'stays on' for a prolonged time. Once these challenges are met in more animal studies, this approach could be tried in humans to slow the progression of ALS. Bohn's co-authors on the study were M. Hasan Mohajeri, Children's Memorial Institute of Education and Research, and Denise A. Figlewicz, University of Rochester Medical Center, Rochester, N.Y. This study was supported by a gift from the Shaw Foundation with help from the Swiss National Science Foundation and National Institutes of Health grants NS31957 and NS34101.